Publications by authors named "Kaoru Ogawa"

302 Publications

Comparison of Drug Availability in the Inner Ear After Oral, Transtympanic, and Combined Administration.

Front Neurol 2021 19;12:641593. Epub 2021 Aug 19.

Department of Otolaryngology Head and Neck Surgery, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

Although combination of oral and transtympanic drug therapy (CT) has been proved more effective and safer for idiopathic sudden sensorineural hearing loss (ISSNHL) by some clinical trials, there are few laboratory researches on the pharmacokinetics in the inner ear following CT on account of structural limitations of the inner ear. The aim of the present study was to investigate the pharmacokinetic behaviors of CT in the inner ear of mice. Eighteen transgenic mice which express luciferase in cochlear spiral ganglion cells were divided into oral administration (OR) group, transtympanic injection route (TT) group and CT group, and luciferin was delivered into the inner ear of these mice through oral, transtympanic or combined routes, respectively. A new imaging system was used to observe luciferin/luciferase signals and the compare the pharmacokinetics of different administration routes in the inner ear of mice. Bioluminescence signals were observed in the inner ear 3.3 ± 2.6 min after CT, significantly earlier than that of OR group (15.8 ± 7.4 min). CT owned the longest reaching-peak time and largest area under the curve (AUC) among three groups. Compared to TT, CT had longer biological half-life and higher AUC value, but did not displayed stronger peak value. There were significant differences in the peak values between OR group and TT group and between OR group and CT group. This study suggests that the OR route is less effective than the TT or CT route, and combination of OR and TT can deliver more drugs into the inner ear and confer a longer therapeutic window, but cannot increase drug intensity.
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http://dx.doi.org/10.3389/fneur.2021.641593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420880PMC
August 2021

Labyrinthine destruction caused by inflammatory pseudotumor of the temporal bone: A report of three cases and review of the literature.

Laryngoscope Investig Otolaryngol 2021 Aug 25;6(4):857-865. Epub 2021 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery Keio University School of Medicine Tokyo Japan.

Background: Inflammatory pseudotumors (IPTs) are rare, idiopathic, and inflammatory lesions that are histopathologically benign. Here, we present three cases of labyrinthine destruction caused by an IPT.

Methods: The first patient was a 74-year-old male with a mass lesion extending from the inner ear to the external ear canal. The second patient was a 62-year-old female with a foliated polycystic lesion in the petrous bone on the dorsal side of the left internal auditory canal. The third patient was a 68-year-old female with a mass extending from the inner ear to the middle ear, destroying the semicircular canal and cochlea.

Results: In two cases, we performed surgical resection successfully with no recurrence. In the other case, the lesion showed shrinkage after chemotherapy for colorectal cancer incidentally found during the examination process.

Conclusion: Surgical technique and indication for IPT should be based on the location and function of the lesion. In addition, there is room to consider pharmacotherapy as a treatment option for IPT of the temporal bone.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356880PMC
August 2021

Trapezius muscle branch of the spinal accessory nerve without penetrating the sternocleidomastoid muscle as a pitfall in neck dissection: prevalence in a Japanese institution and a protocol for the prevention of iatrogenic injury.

Acta Otolaryngol 2021 Aug 12;141(8):825-829. Epub 2021 Aug 12.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University, Tokyo, Japan.

Background: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM).

Aims/objectives: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND.

Materials And Methods: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively).

Results: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality.

Conclusions And Significance: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.
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http://dx.doi.org/10.1080/00016489.2021.1954688DOI Listing
August 2021

Effectiveness of hearing aids in treating patients with chronic tinnitus with average hearing levels of <30 dBHL and no inconvenience due to hearing loss.

Acta Otolaryngol 2021 Aug 7;141(8):773-779. Epub 2021 Aug 7.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Background: The effectiveness of hearing aids for tinnitus patients without hearing loss in conversation-comprehension range and inconvenience in daily communication is unknown.

Objective: We aimed to evaluate their therapeutic effect.

Materials And Methods: We included 91 patients with average hearing levels <30 dBHL. To determine the effects, self-reported questionnaires were used. Data were collected at the entry and 3 months ( = 91) and 1 year ( = 70) after treatment initiation.

Results: All scores (mean ± standard deviation) decreased significantly ( < 0.0001) from before treatment to 3 months and 1 year after treatment: tinnitus handicap inventory score: from 56 ± 21 to 17 ± 17 and 13 ± 15; visual analogue scale (VAS) score for tinnitus loudness: from 71 ± 20 to 31 ± 26 and 28 ± 29; VAS score for tinnitus annoyance: 79 ± 20 to 27 ± 25 and 26 ± 30, respectively. Approximately 90% of patients noticed improvements in tinnitus annoyance and loudness, as determined by the questionnaires regarding subjective symptom improvement.

Conclusions: Hearing aids may be useful for tinnitus patients without hearing loss and inconvenience in daily communication.

Significance: Our findings provide a treatment option for tinnitus patients with an average hearing level of <30 dBHL.
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http://dx.doi.org/10.1080/00016489.2021.1957145DOI Listing
August 2021

Dynamic Spatiotemporal Expression Changes in Connexins of the Developing Primate's Cochlea.

Genes (Basel) 2021 Jul 16;12(7). Epub 2021 Jul 16.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.

Connexins are gap junction components that are essential for acquiring normal hearing ability. Up to 50% of congenital, autosomal-recessive, non-syndromic deafness can be attributed to variants in , the gene that encodes connexin 26. Gene therapies modifying the expression of connexins are a feasible treatment option for some patients with genetic hearing losses. However, the expression patterns of these proteins in the human fetus are not fully understood due to ethical concerns. Recently, the common marmoset was used as a primate animal model for the human fetus. In this study, we examined the expression patterns of connexin 26 and connexin 30 in the developing cochlea of this primate. Primate-specific spatiotemporal expression changes were revealed, which suggest the existence of primate-specific control of connexin expression patterns and specific functions of these gap junction proteins. Moreover, our results indicate that treatments for connexin-related hearing loss established in rodent models may not be appropriate for human patients, underscoring the importance of testing these treatments in primate models before applying them in human clinical trials.
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http://dx.doi.org/10.3390/genes12071082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307058PMC
July 2021

Patterns of hearing changes in women and men from denarians to nonagenarians.

Lancet Reg Health West Pac 2021 Apr 24;9:100131. Epub 2021 Mar 24.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku, Tokyo 160-8582, Japan.

Background: Hearing loss needs to be diagnosed and treated early, especially in older individuals, since presbycusis potentially increases the risk of depression and dementia. However, standard data on hearing thresholds across the life-span in Japanese individuals are lacking.

Methods: In a retrospective consecutive sample of 10681 native-Japanese speakers (37.3% men; 10-99 years; left-right hearing threshold difference of <15 dB for all tested pure tones; free of external, middle, or inner ear disease), we determined standard age-decade and sex-specific pure-tone air-conduction (125, 250, 500, 1000, 2000, 4000, and 8000 Hz) hearing threshold norms. The main outcome measures were pure-tone averages for both ears by age-decade and sex.

Findings: For participants in their 20s, hearing thresholds at higher frequencies (>1000 Hz) were significantly worse in men than in women. For participants ≥70 years, hearing thresholds at low frequencies were higher in women. Hearing thresholds at 1000, 2000, and 4000 Hz tended to deteriorate, starting in the teenage years through the 50s, with some decades showing significantly worse decline. Sex differences were absent in the youngest and oldest groups.

Interpretation: Standard age- and sex-specific audiometric data reported here for Japanese individuals over nine age-decades are based on the largest dataset analyzed to date. While hearing thresholds of men and women in the very young and the very old age groups were indistinguishable in their cohorts, patterns of hearing changes for other age cohorts differed by direction and sex.

Funding: The authors had no outside funding for this study.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315603PMC
April 2021

Investigation of the hearing levels of siblings affected by a single GJB2 variant: Possibility of genetic modifiers.

Int J Pediatr Otorhinolaryngol 2021 Oct 12;149:110840. Epub 2021 Jul 12.

Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan; Medical Genetics Center, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. Electronic address:

Objective: Variants in GJB2 can cause autosomal recessive deafness (DFNB1). There is evidence for genotype-phenotype correlations of GJB2 variants; however, several genotypes can cause varying levels of hearing loss likely attributable to differences in genetic or environmental background. As siblings share approximately 50% of their genetic background and usually have a common environmental background, analysis of phenotypes of siblings with a specific GJB2 variant may reveal factors relevant to phenotypic variation. There have been no previous analyses of differences in hearing among siblings carrying a single GJB2 genotype. Here, we investigated hearing differences between siblings with a single GJB2 variant, which can cause various levels of hearing loss.

Methods: We examined hearing levels in 16 pairs of siblings homozygous for the c.235delC variant of GJB2. Differences in hearing acuity between sibling pairs were detected by auditory evaluation.

Results: Average differences in acoustic threshold >30 dB were observed between five pairs of siblings, whereas the remaining 11 pairs had average threshold values within approximately 10 dB of one another. Hearing loss varied from moderate to profound.

Conclusion: Our results indicate that auditory acuity associated with homozygosity for GJB2 c.235delC can vary in degree; however, in approximately 70% of younger siblings, it was approximately the same as that in the first child, despite a diverse spectrum of hearing loss among different families. These results suggest that differences in genetic background may modify the phenotype associated with homozygous GJB2 c.235delC.
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http://dx.doi.org/10.1016/j.ijporl.2021.110840DOI Listing
October 2021

Pretherapeutic Predictive Factors for Histological High-Grade Parotid Gland Carcinoma.

Laryngoscope 2021 Jul 10. Epub 2021 Jul 10.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objective: The histological grade of parotid gland carcinoma (PGC) is an important prognostic factor; however, the diagnosis prior to treatment has been challenging to make. This study aimed to investigate whether the pretreatment clinical findings, including hematological inflammatory, nutritional, and immune markers, could predict the histological grade of PGC.

Study Design: Retrospective study.

Methods: We retrospectively enrolled 111 patients with PGC and evaluated the correlation between histological grade and pretreatment clinical findings such as age, sex, tumor staging, facial nerve paralysis, pain or tenderness, adhesion to the surrounding tissues or tumor immobility, and hematological markers.

Results: Sixty patients (54%) were diagnosed with histological high-grade PGC. Univariate analysis revealed that age, T classification, N classification, TNM stage, facial nerve paralysis, adhesion/immobility, C-reactive protein (CRP), and CRP-to-albumin ratio (CAR) were significant predictors of PGC histological grade. On multivariate analysis, high T classification (T3, 4), high N classification (≥1), and elevated CRP (≥0.22 mg/dL) were independent predictors of high-grade PGC.

Conclusions: Pretreatment T classification, N classification, and CRP are significant predictors of the histological grading of PGC. Our results are useful for treatment planning and obtaining appropriate informed consent from the patients before treatment.

Level Of Evidence: 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29728DOI Listing
July 2021

Isolated Bone Recurrence of Medulloblastoma With MYCN Amplification and TP53 Loss: A Case Report.

J Pediatr Hematol Oncol 2021 Jun 16. Epub 2021 Jun 16.

Departments of Pediatrics Anatomic Pathology Neurosurgery Community Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Extraneural recurrence of a medulloblastoma is rare with dismal prognosis. A 9-year-old girl with medulloblastoma was treated with gross total resection followed by a combination of chemotherapy and radiotherapy. Fourteen months after treatment completion, she developed multifocal bone metastases. Despite chemotherapy combined with irradiation, she died 18 months after recurrence due to progressive disease. Fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissue sections revealed MYCN amplification and TP53 loss, consistent with the genetic alterations of a rapidly progressive subgroup of recurrent medulloblastomas. In clinical practice, dismal biological features can be determined using fluorescence in situ hybridization in defective materials.
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http://dx.doi.org/10.1097/MPH.0000000000002234DOI Listing
June 2021

Resection of a Large Cavernous Hemangioma Following Preoperative Embolization in a Child's Temporal Bone.

J Int Adv Otol 2021 May;17(3):269-274

Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Primary intraosseous cavernous hemangiomas (PICHs) in the temporal bone are very rare. Most treated cases are in adult patients, and there are very few reports involving children. To our knowledge, no cases reported have ever actually adopted embolization in children, although several reports recommend preoperative embolization of the feeding arteries. Here, we present a case of a child with a large cavernous hemangioma developing in the temporal bone. The patient was an 11-year-old girl whose chief complaints were hearing loss, aural fullness, and otalgia. Based on imaging, a lymphoma was initially suspected, but extensive arterial bleeding occurred during biopsy under local anesthesia. Angiography was performed to evaluate the blood flow in the tumor, and revealed the middle meningeal artery as a main feeding artery to the tumor. A huge PICH at the temporal bone was successfully resected following preoperative embolization of the feeding artery.
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http://dx.doi.org/10.5152/iao.2021.8755DOI Listing
May 2021

Cyclooxygenase-2 expression is associated with chemoresistance through cancer stemness property in hypopharyngeal carcinoma.

Oncol Lett 2021 Jul 17;22(1):533. Epub 2021 May 17.

Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

Cyclooxygenase-2 (COX-2) is one of the two isoforms of COX, an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. COX-2 is associated with the progression in various types of cancer, and its expression has been associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC). Furthermore, COX-2 expression has been associated with resistance to anticancer drugs. However, the precise mechanism of COX-2 for chemoresistance in HNSCC has not been fully elucidated. The present study aimed to investigate the effect of COX-2 on cancer stem cell (CSC) property and to reveal its effect on chemoresistance using and clinicopathological assays in HNSCC cells and tissues. The current study analyzed the immunohistochemical expression levels of COX-2 and clinicopathological factors using matched samples of pretreatment biopsy and surgical specimens from patients with hypopharyngeal carcinoma who underwent tumor resection with preoperative chemotherapy, including docetaxel. Additionally, the chemoresistance to docetaxel with or without a COX-2 inhibitor (celecoxib) was examined in HNSCC cell lines by MTS assays. To evaluate the association of COX-2 expression with stemness property, the expression levels of CSC-associated genes after exposure to celecoxib were assessed by reverse transcription-quantitative PCR. A sphere formation assay was also performed using ultra-low attachment dishes and microscopic imaging. The immunohistochemical analysis of biopsy specimens revealed a negative association between COX-2 expression in biopsy specimens and the pathological effect of induction chemotherapy in surgical specimens. The cell survival rate under exposure to docetaxel was decreased by the addition of celecoxib. COX-2 inhibition led to downregulation of CSC-associated gene expression and sphere formation. The present findings suggested that COX-2 expression may be associated with chemoresistance through the cancer stemness property, and inhibition of COX-2 may enhance chemo-sensitivity in HNSCC. Therefore, COX-2 may be an attractive target for the treatment of HNSCC.
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http://dx.doi.org/10.3892/ol.2021.12794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161457PMC
July 2021

A case report of Kuttner tumor mimicking a malignant tumor, leading to overtreatment.

Clin Case Rep 2021 May 6;9(5):e04120. Epub 2021 May 6.

Department of Otolaryngology Keio University Hospital Tokyo Japan.

Preoperative diagnosis with multimodal approaches might lead to overtreatment. Cautious understanding of cytology and dynamic contrast-enhanced magnetic resonance imaging is required when a Kuttner tumor is cited as differential diagnosis.
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http://dx.doi.org/10.1002/ccr3.4120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123567PMC
May 2021

Three cases of otitis media caused by Mycobacterium abscessus subsp. abscessus: Importance of medical treatment and efficacy of surgery.

J Infect Chemother 2021 Aug 29;27(8):1251-1257. Epub 2021 Apr 29.

Department of Otolaryngology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. Electronic address:

This study aimed to assess the clinical presentation, antibiotic therapy, surgery, and outcomes in patients with otitis media caused by Mycobacterium abscessus subsp. abscessus and discuss the efficacy of surgery. This is a retrospective case review of three patients diagnosed with otomastoiditis caused by M. abscessus subsp. abscessus. All patients had refractory otorrhea. One patient had granulation tissue in the tympanic membrane. They received medical treatment and underwent surgery. Otorrhea was resolved several months after the initiation of long-term multiantibiotic therapy in all cases. The timing of surgery varied among patients. Before initiating antibiotic therapy, mastoidectomy was performed to achieve definitive diagnosis in two patients, and wound dehiscence developed in these patients. Two patients underwent debridement after the initiation of multiantibiotic therapy. After antibiotic administration, tympanoplasty was performed to improve hearing in one patient. All patients achieved culture negativity after treatment, and no recurrences have been noted. From three cases, it is suggested that the mainstay of treatment for M. abscessus subsp. abscessus is long-term multiantibiotic therapy, and surgery itself may have little effect on achieving ear dryness. Thus, in most patients, drug therapy should be prioritized. Considering postoperative complications, surgery before achieving ear dryness should be avoided, except in emergency cases. In addition, if the diagnosis is not confirmed by repeated bacteriological tests, mastoidectomy should be performed to collect specimens. Tympanoplasty for hearing loss or eardrum perforation is recommended after discontinuation of medications.
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http://dx.doi.org/10.1016/j.jiac.2021.04.012DOI Listing
August 2021

Inner ear salivary gland choristoma extending to the middle ear with congenital profound hearing loss and facial palsy: a case report.

J Otolaryngol Head Neck Surg 2021 Apr 15;50(1):25. Epub 2021 Apr 15.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Background: Salivary gland choristoma (SGCh) is a rare benign tumor reported in several unusual sites, such as the gastrointestinal tract, the optic nerve, and the internal auditory canal, but never reported in the inner ear.

Case Presentation: An 8-year-old girl with a history of left profound congenital hearing loss presented to us with ipsilateral progressive severe facial nerve palsy (House-Brackmann Grade VI). The left tympanic membrane was swollen with a pulsatile tumor. Radiological investigations revealed a multilocular tumor in the inner ear extending into the middle ear and internal auditory canal (IAC). We performed a partial resection of the tumor by transmastoid approach to preserve the anatomical structure of the facial nerve. The tumor was pathologically diagnosed as SGCh. Two years after surgery, her facial function recovered to House-Brackmann Grade II and the residual tumor did not show regrowth on MRI.

Conclusions: Although the natural course of this rare tumor is unknown, a partial resection is an acceptable treatment procedure when functional recovery of the facial nerve is anticipated.
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http://dx.doi.org/10.1186/s40463-021-00511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051108PMC
April 2021

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

Auris Nasus Larynx 2021 Dec 26;48(6):1054-1060. Epub 2021 Mar 26.

Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.

Objective: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue.

Methods: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study.

Results: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred.

Conclusion: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.
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http://dx.doi.org/10.1016/j.anl.2021.02.007DOI Listing
December 2021

Delayed facial palsy after cochlear implantation caused by reactivation of Herpesvirus: A case report and review of the literature.

Auris Nasus Larynx 2021 Mar 15. Epub 2021 Mar 15.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.

Cochlear implantation has many complications; however, delayed facial palsy is relatively rare. In this report, we present the case of a 60-year-old woman with delayed facial palsy after cochlear implantation. Eleven days after the operation, the patient complained of right facial palsy (Yanagihara score 6, House-Brackmann [HB] grade VI). Herpes virus reactivation and local bacterial infection were considered as possible causes of the facial paralysis. A blood test revealed an increase in viral antibody titer, and the patient was diagnosed as having herpes virus reactivation. She was treated with antiviral therapy for the facial palsy until resolution. Slight mouth weakness continued even at 1.5 months (Yanagihara score 34, HB II) but eventually resolved at 3 months (Yanagihara score 40, HB I). Delayed facial palsy is a rare but serious complication that can occur with viral reactivation regardless of the competence of the surgical procedure. Therefore, it is important to inform patients preoperatively regarding the risk of not only immediate but also delayed postoperative facial paralysis.
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http://dx.doi.org/10.1016/j.anl.2021.03.001DOI Listing
March 2021

Risk factor for cerebrospinal fluid leak after endoscopic endonasal skull base surgery: a single-center experience.

Acta Otolaryngol 2021 Jun 18;141(6):621-625. Epub 2021 Mar 18.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Japan.

Background: One of the major complications in endoscopic endonasal skull base surgery (EESBS) is postoperative cerebrospinal fluid (CSF) leaks. Recently, EESBS has been applied to various skull base diseases as well as more complicated cases influenced by previous treatment with or without various comorbidities.

Aims/objectives: This study aimed to assess the factors that influence the results of postoperative CSF leak after EESBS with mixed patient backgrounds.

Materials And Methods: We conducted a retrospective analysis of the clinical records of patients undergoing EESBS in our institution from 2012 to 2017.

Results: Out of a total of 230 cases of EESBS, 11 (4.8%) suffered from postoperative CSF leakage. The rate of CSF leakage for pituitary adenoma, Rathke's cleft cyst, chordoma, and meningioma was 3.5%, 0%, 3.6% and 8.0%, respectively. Multiple variate analysis revealed that repeated surgery ( = .008) and intraoperative CSF leak ( = .044) were significant risk factors for postoperative CSF leakage.

Conclusions And Significance: The rate of postoperative CSF leakage in this study was comparable to previous reports, and repeated surgery may increase postoperative CSF leakage. The surgical strategy for tumor removal as well as skull base reconstruction should be given careful consideration according to tumor pathology and the patient's condition.
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http://dx.doi.org/10.1080/00016489.2021.1900600DOI Listing
June 2021

Cut-off score of the Khalfa Hyperacusis Questionnaire with 10 selected items.

Int J Audiol 2021 Mar 18:1-6. Epub 2021 Mar 18.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objective: In the management of hyperacusis, the hyperacusis questionnaire (HQ) is a frequently used measure. It is comprised of 14 items, with a total score of 42 points. We have developed the Japanese version of the HQ, but the validity of the factors has not been considered. This study was performed to re-evaluate the HQ to confirm its validity and reliability.

Design: Exploratory factor analysis was performed and we removed the problematic items with low factor loadings and re-evaluated the reliability and validity.

Study Sample: Patients with hyperacusis (n = 109) were included. Hyperacusis was confirmed based on the patients' complaint of "intolerance to sound". Patients without hyperacusis but with tinnitus and/or hearing loss (n = 103) were also included.

Results: Items 1, 5, 6, and 11 had low factor loadings; therefore, we removed these four items. The HQ with 10 items had high internal consistency reliability (Cronbach's α = 0.926). The mean total scores for the patients with and without hyperacusis were 16.3 and 4.0, respectively; the inter-group difference was statistically significant. We found the best score that maximised sensitivity and specificity was 8.

Conclusions: The HQ with 10 items, up to 30 points and a cut-off score of 8 is appropriate for classifying hyperacusis.
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http://dx.doi.org/10.1080/14992027.2021.1894491DOI Listing
March 2021

Endoscopic Endonasal Transinfraturbinate Approach With Nasoseptal Window for Removal of the Pterygopalatine Fossa Tumor.

J Craniofac Surg 2021 Mar-Apr 01;32(2):716-718

Department of Neurosurgery.

Abstract: Recent advances in endoscopic intranasal technology have allowed for a safe approach to the pterygopalatine fossa lesion. However, we consider that there is still scope of improvement to approach a broader area with better operability and minimal invasiveness. A 51-year-old man underwent endoscopic endonasal surgery due to the recurrence of chordoma at the left pterygopalatine fossa. To access the lower and lateral part of the pterygopalatine fossa, we performed endoscopic endonasal transmaxillary removal via an inferior turbinate incision. During surgery, a wide operative field and good operability could be secured by inserting an endoscope from the right nostril through a window of the nasal septum. Subtotal removal of the tumor was achieved without any complication during the surgery. Endoscopic endonasal transinfraturbinate approach with nasoseptal window was effective in the removal of the pterygopalatine fossa tumor because it is less invasive and provides a good surgical view with better operability.
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http://dx.doi.org/10.1097/SCS.0000000000006979DOI Listing
June 2021

Transoral Removal of Tumors of the Dorsal Aspect of the Soft Palate: A Technical Note.

Laryngoscope 2021 09 26;131(9):2011-2014. Epub 2021 Feb 26.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1002/lary.29457DOI Listing
September 2021

Effectiveness of Hearing Aid Treatment in Patients with Chronic Tinnitus: Subscale Evaluations Using the Tinnitus Functional Index and Factor Analysis.

J Int Adv Otol 2021 Jan;17(1):42-45

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objectives: The tinnitus functional index (TFI) is becoming a new international gold standard for tinnitus assessment. This study aimed to evaluate the efficacy of hearing aids for chronic tinnitus, using the Japanese version of the TFI, while focusing on its subscales.

Materials And Methods: This is a retrospective study. A total of 21 patients with chronic tinnitus were included. All participants were treated with hearing aids for at least 12 months. They answered the TFI and tinnitus handicap inventory (THI) at the first visit and 12 months later. We analyzed each TFI subscale score and the overall scores of TFI and THI.

Results: The overall TFI score decreased significantly after treatment (p=0.005) with moderate effect size (d=0.70). The scores of the intrusive, sense of control, sleep, and emotional subscales decreased significantly after the treatment. Large effect sizes were found in the intrusive and sense of control subscales (d=1.33 and d=1.25, respectively).

Conclusion: Hearing aids are highly effective for improving the intrusive and sense of control subscales in patients with tinnitus. Identifying better treatments for the small effect size subscales and combining these with the use of hearing aids could achieve a higher therapeutic effect with better outcomes.
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http://dx.doi.org/10.5152/iao.2020.9161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901423PMC
January 2021

Hydroxyapatite Prostheses in Endoscopic Transcanal Stapes Surgery for Otosclerosis Cases.

Ear Nose Throat J 2021 Feb 2:145561321989143. Epub 2021 Feb 2.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objectives: Hydroxyapatite is a commonly used material for medical applications due to its excellent biocompatibility. We use hydroxyapatite prosthesis for the reconstruction of the ossicular chain in stapes surgery. In this study, we report a case series of endoscopic ear surgery using a basket-type hydroxyapatite prosthesis.

Methods: We retrospectively examined 8 cases of endoscopic transcanal stapes surgery using hydroxyapatite prostheses. We evaluated the postoperative results and complications.

Results: The average postoperative air-bone gaps were within 10 dB in all cases. Postoperative sensorineural hearing loss was not observed in any case. There was an intraoperative complication with the chorda tympani in 1 patient. We were able to preserve the chorda tympani of all patients, including this case. Postoperative transient dizziness and transient taste disorder were observed in 50% of cases. No other complications, including facial nerve palsy, tympanic membrane perforation, or postoperative infection, were observed.

Conclusions: The postoperative results and complications were comparable to those of surgery under a microscope. The hydroxyapatite prosthesis could be a possible alternative for the piston-type titanium or polytetrafluoroethylene prosthesis.
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http://dx.doi.org/10.1177/0145561321989143DOI Listing
February 2021

Efficacy of cartilage conduction hearing aids in children.

Int J Pediatr Otorhinolaryngol 2021 Mar 16;142:110628. Epub 2021 Jan 16.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objectives: Cartilage conduction hearing aids (CC-HAs) are novel hearing aids that use the third hearing pathway of cartilage conduction. We assessed the efficacy of CC-HAs and the hearing effects and safety of additional tape compression over the transducer in children with hearing loss.

Methods: The patients (n = 42) underwent a one-month free trial of CC-HAs. Forty of them were patients with auditory canal atresia or stenosis. CC-HA-aided and unaided hearing thresholds (48 fitted ears) were determined using standard audiograms, after which participants could choose to purchase the device or not. We calculated the purchase rates and compared the patient characteristics between the purchase and non-purchase groups along with the purchase reason (or not). We applied additional tape compression over the CC-HA transducer and assessed the hearing effects and side effects.

Results: CC-HA led to hearing improvements at all frequencies. Overall, 72.92% of participants purchased a CC-HA after the trial. By applying additional tape compression over the CC-HA transducer, the stability and hearing gains were improved mainly at low frequencies, and no side effects such as dermatitis were observed.

Conclusions: CC-HAs are efficacious in producing hearing improvements in children, especially in patients with atresia or canal stenosis who cannot use air conduction hearing aids. Furthermore, we found that the additional tape compression over the transducer was an easy and a safe method for improving the hearing effects and stability of the CC-HA.
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http://dx.doi.org/10.1016/j.ijporl.2021.110628DOI Listing
March 2021

Sudden sensorineural hearing loss in patients with vestibular schwannoma.

Sci Rep 2021 01 21;11(1):1624. Epub 2021 Jan 21.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.

Clinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.
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http://dx.doi.org/10.1038/s41598-020-80366-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820278PMC
January 2021

Effective sound therapy using a hearing aid and educational counseling in patients with chronic tinnitus.

Auris Nasus Larynx 2021 Oct 15;48(5):815-822. Epub 2021 Jan 15.

Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.

Objective: This study aimed to assess the effectiveness of our sound therapy with appropriate hearing aid fitting and periodic hearing aid adjustment in patients with chronic tinnitus.

Methods: We conducted a retrospective study. The study included 490 individuals who received treatment with hearing aids for chronic tinnitus at least for 3 months. To determine the effects of tinnitus on patients' quality of life, the participants completed a series of questionnaires, including the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS) for loudness and annoyance, and questionnaires of subjective symptom improvement. Data were collected at entry and 3 months and 1 year after treatment initiation.

Results: All 490 participants completed the questionnaires at 3 months; however, only 312 completed them at 1 year. The mean ± standard deviation THI score before treatment decreased significantly at 3 months (490 participants: 53 ± 25 to 11 ± 16 and 312 participants: 55 ± 24 to 12 ± 16) and 1 year (55 ± 24 to 9 ± 14) (P < 0.01). The mean VAS score for tinnitus loudness before treatment decreased significantly at 3 months (490 participants: 70 ± 22 to 25 ± 27 and 312 participants: 71 ± 22 to 27 ± 26) and 1 year (71 ± 22 to 21 ± 28) (P < 0.01). In addition, the mean VAS score for tinnitus annoyance before treatment decreased significantly at 3 months (490 participants: 75 ± 26 to 20 ± 26 and 312 participants: 75 ± 25 to 23 ± 27) and 1 year (75 ± 25 to 17 ± 26) (P < 0.01). Approximately 80% of patients noticed improvements in their tinnitus annoyance and loudness, as determined by their responses to the questionnaires of subjective symptom improvement.

Conclusion: The results of this study suggest that treatment with sound therapy may ameliorate the symptoms of chronic tinnitus associated with hearing loss.
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http://dx.doi.org/10.1016/j.anl.2021.01.001DOI Listing
October 2021

Early hearing improvement predicts the prognosis of idiopathic sudden sensorineural hearing loss.

Eur Arch Otorhinolaryngol 2021 Jan 2. Epub 2021 Jan 2.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, 160-8582, Japan.

Purpose: To determine pre- and post-treatment factors that are useful for predicting the prognosis of hearing improvement in idiopathic sudden sensorineural hearing loss (ISSHL).

Methods: This retrospective study included 332 patients with ISSHL. Patients received intravenous steroid treatment (prednisolone sodium succinate; 120 mg/day followed by dose tapering). Complete recovery of hearing levels was defined as a final pure-tone audiometry of ≤ 20 dB HL or the same level as the contralateral ear. Patients' age; sex; side of hearing loss; initial hearing level; days from onset to treatment; presence of vertigo, diabetes, and hypertension; and hearing improvement on days 3-4 and 6-7 after treatment initiation were analyzed as potential prognostic factors.

Results: Overall, 109 patients (32%) had complete recovery. Results of the multivariate logistic regression model identified age (odds ratio [OR] = 0.974), initial hearing level (OR = 0.949), vertigo (OR = 0.409), and hearing improvement on days 6-7 after treatment initiation (OR = 1.11) as significant independent predictors of complete recovery. Age ≥ 60 years, initial hearing level ≥ 72.5 dB HL, and vertigo contributed to poor prognosis. Patients without these three factors and a hearing improvement of ≥ 10 dB HL on days 6-7 post-treatment had a complete recovery rate of 80%. Only 1.5% of the patients with 2-3 of these factors and a hearing improvement of < 10 dB HL on days 6-7 after treatment initiation achieved complete recovery.

Conclusion: Age, initial hearing level, vertigo, and hearing improvement on days 6-7 after treatment initiation were independent predictors of hearing recovery in ISSHL.
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http://dx.doi.org/10.1007/s00405-020-06532-4DOI Listing
January 2021

Management of tinnitus in patients with vestibular schwannoma who underwent surgical resection.

Eur Arch Otorhinolaryngol 2021 Jan 1. Epub 2021 Jan 1.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 160-8582 Shinanomachi 35, Shinjuku-ku, Tokyo, Japan.

Purpose: To evaluate tinnitus and its management in patients with vestibular schwannoma (VS) who underwent surgery, we investigate the effect of surgical approach or residual hearing on tinnitus severity and the effects of intervention for tinnitus including educational counseling, sound therapy using hearing aids (HAs), and medication (selective serotonin reuptake inhibitors, and SSRIs).

Methods: Seventy-one subjects of VS patients who underwent surgery were included. Their tinnitus severity was evaluated using the Japanese version of the Tinnitus Handicap Inventory (THI). The relationships between postoperative THI scores and surgery types or residual hearing levels were examined. We also examined longitudinal changes in THI scores and the efficacy of the intervention.

Results: Surgery approach, hearing preservation or hearing loss surgery, and residual hearing levels were not significantly related to the postoperative tinnitus severity. In 71 cases, 45 cases did not require any management for tinnitus. On the contrary, 26 patients had at least one episode of tinnitus distress (THI score was greater than or equal to 18). Educational counseling alone was found to be effective in 17 cases out of the 26 cases, and the remaining 9 cases required more intervention than educational counseling alone. We selected sound therapy with HA for 7 cases and administration of SSRI for 2 cases, which was found to be highly effective in 8 cases.

Conclusion: Based on the present study, we consider that appropriate management may be possible for tinnitus in the majority of VS patients who underwent surgery.
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http://dx.doi.org/10.1007/s00405-020-06531-5DOI Listing
January 2021

A Case of Periaortic Lymphoma Mimicking Complicated Type B Acute Aortic Dissection: A Pitfall in the Endovascular Surgery Era.

Ann Vasc Dis 2020 Sep;13(3):312-315

Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine.

We report a case of periaortic lymphoma mimicking Stanford type B acute aortic dissection treated for impending rupture by thoracic endovascular aortic repair. Although no endoleak was detected, the aneurysm enlarged continuously. Repeat computed tomography scans showed that an aortic aneurysm-like structure around the stent graft had enlarged irregularly. Histopathological examination revealed diffuse large B-cell malignant lymphoma. Post-chemotherapy, the aneurysm-like structure disappeared without any fistula or rupture. In open surgery, differentiating between aneurysms and malignancy is easy under direct vision; however, in the endovascular surgery era, this is a pitfall because no surgical specimen of the lesion can be obtained.
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http://dx.doi.org/10.3400/avd.cr.20-00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751082PMC
September 2020

Endoscopic Endonasal Management of Pterygopalatine Fossa Tumors.

J Craniofac Surg 2021 Jul-Aug 01;32(5):e454-e457

Department of Otolaryngology, Head and Neck Surgery.

Abstract: Surgical removal of pterygopalatine fossa (PPF) tumors with endoscopic endonasal approach is still challenging. The present study aimed to evaluate our endoscopic endonasal management of PPF tumors based on the tumor pathology and purpose of the surgery. This comprised both a single nostril approach for biopsy and a binostril approach for complete resection of benign and noninfiltrating tumors. Based on this strategy, 12 patients underwent endoscopic endonasal surgery for PPF tumors between 2013 and 2018. The patients' data were analyzed retrospectively to demonstrate the significance of our treatment scheme. The surgery was terminated only after taking a biopsy specimen in 6 patients. Other 6 patients underwent gross total resection or bulk tumor reduction. Final pathological diagnosis was malignant in 6 cases and benign in the remaining 6. Post-operative treatment was needed in 7 patients. Four operations for the 6 patients who underwent either debulking or radical surgery were performed by the binostril approach; while 5 surgeries for the 6 biopsy patients were performed by the single nostril approach. Postoperative complications were tolerable. Endoscopic resection should be adopted preferentially for benign tumors that can be removed in a piecemeal fashion. However, as most malignant tumors were impossible to resect with a negative margin, priority should be given to tumor biopsy using an endoscopic approach, which is less invasive than an open approach, and an appropriate treatment customized to the pathological diagnosis should be administered.
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http://dx.doi.org/10.1097/SCS.0000000000007292DOI Listing
July 2021

Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice.

Biochem Biophys Res Commun 2021 01 5;534:921-926. Epub 2020 Nov 5.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. Electronic address:

Mammalian auditory hair cells are not spontaneously replaced. Their number and coordinated polarization are fairly well-maintained and both these factors might be essential for the cochlear amplifier. Cell cycle regulation has critical roles in regulating appropriate cell size and cell number. However, little is known about the physiological roles of the Hippo pathway, which is one of the most important signaling cascades that regulates cell growth, differentiation, and regenerative capacity in the cochlear sensory epithelium. Herein, we investigated the in vivo role of the large tumor suppressor 1 (LATS1), an essential kinase in the Hippo/yes-associated protein pathway, in the cochlea using the LATS1 knockout mice. LATS1 was expressed in hair cells and supporting cells. It was strongly expressed on the surface of the cuticular plate of the organ of Corti. We found that LATS1 knockout caused congenital hearing loss due to the irregular orientation and slightly reduced number of hair cells, whereas the number of supporting cells remained unchanged. On the surface of the hair cells, the kinocilium and stereocilia were dispersed during and after morphogenesis. However, the expression of the receptor-independent polarity regulators, such as Par3 or Gαi, was not affected. We concluded that LATS1 has an indispensable role in the maturation of mammalian auditory hair cells, but not in the development of the supporting cells, and thus, has a role in the hearing acquisition.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.073DOI Listing
January 2021
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